The invention relates to an article.
An article as described herein has a surface that is modified in order to reduce protein and cell adhesion and can thus be described as antifouling-coated surface.
Biofouling on material surfaces in the biological, medical or diagnostic field is a major problem that can result in inflammation, cell adhesion, irritation of the surrounding tissue, and improper function of devices in vivo and in vitro [1, 1a, 2]. Therefore, improving the bioinert and antifouling ability of material surfaces in contact with biofluids plays an important role, e.g. in medical engineering. Medical implants for example are manufactured from diverse material classes in order to fulfil the specific criteria of their mechanical and biochemical requirements. Polymers, metals, ceramics and others are commonly used for the production of surgical and orthopaedic screws, plates, dental implants, artificial limbs, stents, or drug eluting devices. Some of these are desired to stay inside the body for the lifetime of the patient. However, most materials exhibit a significant degree of bioincompatibility on the long term leading to serious side effects like improper function of devices, in particular biosensors, rejection of implants, and life threatening restenosis of arterial stents.
In order to overcome these issues and to improve the biocompatibility of materials a commonly applied strategy is to coat the surface of the material with a stealth, biocompatible material [3]. Most commonly polyethylene glycol (PEG), a linear polyether polymer which is known since decades to improve the biocompatibility of materials surfaces is employed besides others such as polyvinylpyrrolidone (PVP) [4], oligo(ethylene glycol) (OEG) [5], albumin [6], heparin [7] and dextran [8].
Thereby, single step of monolayer formation [9,10] and multiple step surface modification approaches [11,12] are the most common methods to yield bioinert surfaces. Monolayers are normally created by the chemisorption of head anchors onto substrates followed by a slow organization of the tail groups [13]. Macromolecular tail groups may limit the further adsorption of other feasible adsorbates to form a dense single monolayer due to steric crowding [14].
In addition, the respective bioinert polymer for surface modification has to be modified with a surface specific and reactive anchor that allows for the tethering of the polymer to substrate surface. Unfortunately, despite their comparably easy preparation monolayered coatings often lack stability and easily get destructed. In multiple step surface modification adhesive molecule layers are typically employed, for example poly(ethylene imine) [15] and polydopamine [16,17] which both are more substrate-independent since they stick to a variety of materials via electrostatic and van-der-Waals interactions to connect the substrates and the bioinert molecules to build up the antifouling coatings.
However, these chemically active adhesive layers show a significant fouling performance most likely due to their charged nature, which is difficult to be completely shielded by grafting bioinert terminal layers on top of it [18,19].
In order to resolve this contradiction between stable coatings on the one hand, and perfectly bioinert surfaces on the other hand, the preparation of stable, highly effective antifouling coatings remains a great challenge, especially when it comes to substrates that are chemically not easy to modify like most polymeric materials.
In the search for antifouling PEG alternatives, polyglycerol (PG) and its derivatives have been identified [20,21] as strong and potent candidates because of their easy accessibility and higher thermal and oxidative stability than PEG. Surface bound hyperbranched polyglycerol (hPG), which has a highly branched architecture consisting of a flexible aliphatic polyether backbone with hydrophilic surface groups, shows similar or better protein resistant performance than PEG-coated surfaces. Gold and glass surfaces have been modified by hPG monolayers and were classified as highly protein-resistant materials [20,21]. But it still remains a challenge to immobilize hPG on a broad range of different material surfaces, like titanium dioxide and commodity plastics, by using the same surface linker group.
One substrate-independent coating approach is bioinspired and based on a mussel adhesive peptide rich in the amino acid L-3,4-dihydroxyphenylalanine (DOPA), an amino acid that bears a catechol motive which is believed to be responsible for both adhesive and crosslinking characteristics [22]. Catechol itself has been proven to be a powerful anchor for surface modification [16,17,23-26]. Catechol groups, which are found in mussel adhesive proteins [22,27] and bacterial siderophores [28,29] can adhere on virtually almost any material surface. Although the mechanistic adhesion details are still not well understood, previous studies have proposed several mechanisms for different kinds of substrates.
Some research has proposed that a charge-transfer complex could be formed between the catechol and a TiO2 surface [30] or that a hydrogen bonding could be formed between the catechol and mica surface [31]. Also van der Waals forces between the catechol and polymer surfaces [32] and covalent bonds on nucleophile containing surfaces have been discussed [33].
At least three catechols are required in the anchor group to effectively and stably immobilize macromolecules on substrates [34,35]. Thus, a number of new catecholic anchor groups have been developed, including 3,4-dihydroxyphenylalanine (DOPA) contained decapeptide [36,37], DOPA short peptides [34,38], pentapeptide of alternating DOPA and lysine residues [24,39], catechol derivatives [40,41], catechol side chains [42], oligo-catechol [35], tripodal catecholates [43], and polyDOPA [44].
It is not easy to prepare these catecholic anchor groups, because they require challenging organic synthesis or solid phase synthesis for the DOPA containing peptides. Thus, so far all catechol bearing anchor groups have been synthesized on a milligram scale only, which is insufficient for many coating applications. In addition, in most cases a coupling step of the bioinert or bioactive compound or polymer to the catecholic anchor moiety is required.